The reasons why gingivitis progresses to periodontal disease with pocket formation are uncertain. Apical migration of epithelium invariably accompanies this process but is a poorly understood phenomenon. The junctional epithelium (JE) is unusual in that it forms an attachment to the tooth and recent work has indicated that it is also unusual in other ways. It has a pattern of differentiation associated with the co-expression of markers typical of both simple and stratifying epithelia. This is unlike other oral mucosal epithelia but is similar to some odontogenic epithelia. There is evidence to suggest that this epithelial phenotype is associated with passive non-migratory behavior and shows little change in the presence of inflammation. It may thus be resistant to activation by inflammatory cytokines and such behavior would tend to stabilize the dento-gingival region and prevent inflammation from initiating pocket formation. We will investigate how the unusual phenotype of junctional epithelium is established and maintained, and how it differs in its behavior from oral gingival epithelium (OGE). Cell culture methods have been developed for in vitro growth of JE and OGE and have demonstrated maintenance of intrinsic differences between a) their growth and behavior, and b) their patterns of phenotypic expression of keratins, blood group antigens and other markers. Using such defined culture systems, we will investigate the responses of JE and OGE to cytokines associated with epithelial growth control and to retinoic acid. We will also examine their patterns of expression of cytokines and of cytokine and retinoic acid receptors. Using an "organotypic" system for co-culture of keratinocytes and fibroblasts, we will determine the ability of regionally-differing fibroblasts to modulate the basic epithelial phenotype and the roles that cytokines and retinoids play in such interactions.. The data will be correlated to determine the nature of the differences between these epithelia and will be used to assess the role of inflammation in loss of stability of the dento-gingival complex.